Molecular imaging is gaining popularity in the scientific community as a means of tracking the progression of disease in animals that may also occur in humans. Techniques for imaging include, e.g., X-ray imaging, optical imaging (namely bioluminescent and fluorescent), photo-acoustic imaging, etc. Using such techniques, snapshots of disease states can be collected to monitor the development of abnormalities, such as tumors, in animals over time. Planar imaging modalities acquire images in two-dimensional (2D) space, but the utility of such imaging is hampered by variability created by the total signal intensity in given regions of interest due to the position of the target with respect to the detector. Signal intensity from the target being imaged is related to multiple factors including, but not limited to, the distance and relationship of the signal source to the detector or cooled charge-coupled device (CCD) camera and the location of the signal within the animal.
As light passes through tissue, it scatters due to the inherent absorption properties of blood, muscle, and fat. Thus, tissue acts as a non-homogenous medium for light propagation. Scattering of light doubly affects fluorescence imaging methods, wherein a probe located within an animal must receive enough energy from this diffuse excitation light beam to allow it reach the excited state and produce emitted photons of light which are seen at a Stokes shifted wavelength. As such, both excitation and emission light scatter as they travel to and from the target. As a result, the orientation of the internal target and the CCD camera or detector is a critical determinant of signal intensity, as the more tissue that the light must transverse through, the more the diffusion and loss of signal caused.
To address this problem, researchers often acquire images from multiple orientations of the subject in order to more accurately localize the source of the signal, e.g., an optical signal (bioluminescent/fluorescent signal). The term “subject” will heretofore be used to denote a collection of potential objects being imaged including but not limited to either small animals, tissues, bone, and/or imaging phantoms. However, this manual manipulation of the subject relative to the camera only allows for a typical maximum of four orientations (dorsal, ventral, and each sagittal), and is often not easily reproducible in the same subject, e.g., mouse, monitored over a span of week to months. As a result, these changes in orientation are inherently subjective.
There is distinct advantage to being able to understand the source of a signal in an animal from all angles to eliminate inherent biases. Researchers have been forced to flip and reposition an animal for each image acquisition. This is a tedious process that expands logarithmically the time required of the animal to be under anesthesia, thus threatening the animal's health.
Other imaging modalities, such as fluorescence molecular optical projection, photo-acoustic/opto-acoustic, and positron emission tomographies, have been developed in an attempt to alleviate some of these inherent scattering problems that hamper in vivo optical imaging. For fluorescence molecular tomography (FMT) and positron emission tomography (PET) these concerns are addressed by multiple detectors or by movement of the detector around the subject, respectively. In the case of FMT and optical projection tomography, the fluorescence derived from the target is reconstructed by use of a trans-light projection to correct for the scatter of the signal, thereby creating a single three-dimensional (3D) image of the signal source in a subject. For PET, FMT and optical projection tomography techniques, specialized instrumentation is required to construct a 3D representation of signal from a phantom (or testing platform) or within an animal. The cost for these systems is exponentially higher than “standard optical imaging devices”, forthwith representing the PerkinElmer—IVIS Lumina series, Spectral Imaging—Ami-X, ProteinSimple—AlphaImager HP or FluorChem imagers, or similar top mounted CCD or other detector instruments and thus are frequently unaffordable for many laboratories. Another type of commercially available optical imager is the Bruker/Carestream/Kodak MS In vivo MS FX Pro, In vivo FX Pro or In vivo Extreme imagers, which have a rotational system referred to as Multimodality Animal Rotation System (MARS) (U.S. Pat. No. 8,660,631) that is designed for use with their imagers alone and completely incompatible with above mentioned standard optical imaging devices.
Accordingly, it can be seen that needs exist for a device and method for unobstructed 360 degree imaging of specimens in a simple, inexpensive manner that can be used in these standard optical imaging devices.
It is to the provision of devices and methods for meeting these and other needs that the present invention is primarily directed.